When CPAP Treatment Increases Inflammation in Patients With Obstructive Sleep Apnea

How should clinicians proceed when continuous positive airway pressure (CPAP) has a negative affect on lung health during treatment for obstructive sleep apnea (OSA)?

Neurology Learning Network connected with Sanja Jelic, MD, professor of medicine, Columbia University, to discuss findings in and implications of her study “CPAP may promote an endothelial inflammatory milieu in sleep apnoea after coronary revascularization,” published in eBioMedicine.

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Editor’s note: This piece has been lightly edited for length and clarity.

Brionna Mendoza, Associate Digital Editor, Neurology Learning Network: What led you and your colleagues to conduct this study?

Sanja Jelic, MD: We noticed that a proinflammatory marker angiopoietin-2, which is elevated in untreated patients with OSA compared with healthy controls, increased further with CPAP therapy. This was unexpected, so we repeated this in 2 additional independent patient cohorts and it was confirmed. We then did some reading and discovered that such phenomenon occurs in patients with acute respiratory distress syndrome (ARDS) who have ventilator-induced lung injury. We then concluded that it may be lung distension from CPAP that causes this further increase in inflammation. We tested this in the Randomized Intervention With CPAP in CAD and OSU [(RICCADSA); NCT00519597] cohort and it was confirmed.

Mendoza, NLN: Please briefly describe the study method and your most significant finding(s). 

Dr Jelic: We measured blood biomarkers of lung epithelial and endothelial injury (cells lining the lung spaces and blood vessels in general [including lung blood vessels], respectively) at baseline (before treatment with CPAP) and after 12 months of CPAP in RICCADSA cohort that consists of patients who had a cardiovascular event and underwent revascularization within 6 months of enrollment  (patients with OSA randomized to CPAP vs. no CPAP, and a third group of OSA-free patients). We confirmed that angiopoietin-2 remains elevated in the CPAP group, unlike in the no CPAP and non-OSA groups where it declines naturally as time elapses from the cardiovascular event. Greater levels of this marker Ang-2 were associated with greater mortality in this cohort. We also found that increased levels of a marker of lung injury called soluable receptor of advanced glycation end-products (sRAGE) are associated with worse cardiovascular outcomes in this cohort.

Most interestingly, greater CPAP levels were associated with worse cardiovascular outcomes, suggesting that indeed it might be lung distension that underlies an increase in pro-inflammatory milieu after CPAP treatment. This unexpected finding may counteract the expected benefit of CPAP, which very effectively eliminates episodic hypoxia (low oxygen levels) in OSA. This episodic hypoxia underlies increased cardiovascular risk in OSA and eliminating it would be expected to reduce CV risk. However, 3 large randomized trials showed no reduction in CV risk with CPAP in OSA, and the reasons behind this failure are unclear. We think that our findings shed some light on this issue.

Mendoza, NLN: How do these findings shed light on the potential mechanisms by which CPAP therapy may impact lung endothelial and epithelial inflammation, and what implications do they have for our understanding of the cardiovascular risks associated with OSA treatment?

Dr. Jelic: In addition to the details outlined in my answer to question 2, the implications are that a more conservative CPAP pressure should be considered for treatment of OSA to still exert the benefit of eliminating episodic hypoxia while limiting adverse effects of lung distension.

Mendoza, NLN: What are the next steps for research in this field, and how do you envision your findings influencing the development of future treatment strategies for patients with OSA and cardiovascular disease?

Dr Jelic: It would be useful to compare the effects of the current standard CPAP tressures (4-20 cm H2O) versus lower pressures, such as 4-8 or so, on cardiovascular outcomes and markers of inflammation and lung epithelial/endothelial injury. 

Mendoza, NLN: Which takeaways from this study would you most like to emphasize for audiences on Neurology Learning Network, Psych Congress Network, and Pulmonolgy Learning Network?

Dr Jelic: All medical therapies may have adverse effects, including those considered most benign based on current knowledge. When possible harm signals arise, the medical community should take it seriously and consider how to minimize it. In this case, a more conservative CPAP pressure should be considered for treatment of OSA to still exert the benefit of eliminating episodic hypoxia while limiting adverse effects of lung distension.

Sanja Jelic, MD, is a professor of medicine in the Division of Pulmonary, Allergy, and Critical Care Medicine at Columbia University in New York. She received her MD degree from the University of Zagreb, Croatia, and trained in internal, pulmonary, and sleep medicine at the Albert Einstein College of Medicine and Columbia University in New York. Her research focuses on the molecular mechanisms of endothelial dysfunction in disturbed sleep, including obstructive sleep apnea and sleep deprivation. Dr Jelic was named Herbert Irving Professor at Columbia University and received awards from the American Thoracic Society, the American Academy of Sleep Medicine, and the American Lung Association. Dr Jelic’s work is funded by the NIH/NHLBI, American Heart Association, American Thoracic Society, and American Academy of Sleep Medicine. She is the director of the Center for Sleep Medicine at Columbia University Irving Medical Center.